The clinical features of impaired nerve function arise from disturbances in the structure of the cell body (neuronopathy), its axon (axonopathy), or the myelin coverings of the axon (myelinopathy). Disturbed function of peripheral nerves (neuropathy) can occur when chronic ischemia (associated with vascular disease) or inflammation prevents delivery of critical levels of nutrients and oxygen to the affected nerve fibers. Neuropathies can involve one (mononoeuropathy) or more nerves (polyneuropathy). Neuropathy can affect primarily sensory or motor fibers or may affect both types of fibers (sensorimotor neuropathy).
Reversible symptoms of disrupted nerve conduction occur with localized acute ischemia due to compression of the vascular supply to the affected nerves such as occurs with sitting in one position for an extended period of time. Such conditions are associated with weakness, numbness and paraesthesias or “pins and needles” in the affected limb, which are early clinical signs of peripheral neuropathy. These symptoms are readily relieved with change in position and the restoring of blood flow to the affected area. Similar reversible disturbances of sensory nerve conduction occur with local anesthetics (e.g., cocaine) and with exposure to certain chemicals (e.g., pyrethrins) that impede nerve conduction by disrupting sodium transport across neuronal cell membranes. Small unmyelinated nerve fibers are more susceptible to the effects of local anesthetics and thus these chemicals are ideal for producing anesthesia without paralysis. Metabolic disturbances such as levels of increased blood glucose and metabolites associated with diabetes can also produce a sensorimotor neuropathy.
The neuronopathies are characterized by pathological changes that begin in the cell body. Pyridoxine neurotoxicity is an example of a sensory neturonopathy and is characterized by chromatolysis (dissolution of Nissl substance and margination of the nucleus to the periphery of the cell body) followed by disintegration of the cell body and axon (i.e., necrosis) and its myelin sheath. Regeneration does not occur in the neuronopathies because the cell body is destroyed. Amyotrophic lateral sclerosis, or Lou Gehrig's Disease, (anterior horn cell disease) and polio are examples of motor neuronopathies. In neuronopathy and axonopathy (below) secondary muscle atrophy occurs.
A peripheral nerve fiber that is crushed or compressed undergoes Wallerian degeneration, which is characterized by disintegration of segments of the axons and myelin sheaths distal to the site of injury. The Schwann cells surrounding the severed portion of an axon stop synthesizing new myelin and the existing myelin breaks down to form myelin ovoids. The injured cell soon generates new axons front growth-cones that form at the end of the old axon above the site of injury. The surviving Schwann cells divide and remyelinate the new axon as it grows within the original basal lamina.
Complete transection of the axon and its surrounding connective tissues significantly hampers functional recovery as the axon does not have a preserved basal lamina to direct its growth back toward its original site of innervation. Aberrant collateral sprouting occurs and may be associated with additional functional disturbances due to the development of abnormal patterns of sensorimotor innervation.
Distal central-peripheral axonopathy is a process similar to Wallerian degeneration, in that the axonal continuity is interrupted and secondary demyelination occurs. This can occur as a result of “chemical transection” of the axon with the subsequent disintegration of the axon and myelin sheath distal to the site of the lesion. This pathological process is often preceded by paranodal swellings with associated accumulations of neurofilaments, which are visible on microscopic examination. Longer axons are more vulnerable to the effects of a neurotoxicant induced chemical transection and thus, nerve fibers of the lower extremities are typically affected first. Regeneration occurs with cessation of exposure to the offending neurotoxicant and begins with the proliferation of Schwann cells and the formation of growth cones from which new axonal processes develop.
Myelinopathies are characterized by disintegration of myclin sheath with preservation of the axon. Myelinopathies may be due to toxic exposures, infections, or immune-mediated inflammatory responses (e.g., Guillain-Barre syndrome). Compression of the nerve also disrupts myelin which in turn impedes conduction of nerve impulses and slows nerve conduction velocities. Cardinal features of myelinopathy include segmental demyelination, wherein the myelin of some internodes is damaged with preservation of others. The breakdown of internodal myelin appears as ovoids along the course of the intact axon. Motor nerves are composed of more heavily myelinated fibers than are sensory nerves and thus motor nerves are more susceptible to the effects of trauma and pressure such as entrapment injury that occurs within the carpal tunnel. Remyelination occurs with removal of the offending agent or condition of entrapment. The myelinated nerve is altered by the presence of internodes of different lengths which can affect the conduction characteristics of the peripheral nerve.
One approach that has been suggested is described in U.S. Pat. Nos. 6,936,012; 6,692,444; 6,507,755; 6,379,313; 6,266,558; 6,146,335; 6,132,387; 6,132,386; 5,976,094; and 5,851,191, whose teachings are apparently incorporated in an NC-stat system available from NeuroMetrix, Inc., of Waltham, Mass., and described at http://www.neurometrix.com/products.htm. The NC-stat system consists of the following four components: (1) A battery-powered monitor—The monitor contains the electronic circuitry and software required to provide initiate and control the nerve conduction study, acquire and save patient and test information including the response waveforms, display information on the LCD readout, and transmit data to the docking station. LCD displays include the distal motor latency (DML) value, the distal sensory latency (DSL) value, the Sensory Nerve Action Potential (SNAP) amplitude value, the F-wave latency value, limb indicator (left or right), low battery indicator, the memory slot being used to store the test data, and user messages (menu selections, sensor serial numbers, device status, operator instructions, and error conditions). (2) A docking station used to download the test data to the onCall Information System via an analog phone line. (3) Single-use, disposable biosensors are available for the median motor, ulnar motor, median motor & sensory, ulnar motor & sensory, posterior tibial, deep peroneal and sural nerves. (4) The onCall Information System for automatic generation of the hardcopy patient test report, which includes test results (DML, Compound Muscle Action Potential—CMAP—amplitude, DSL, SNAP amplitude, conduction velocity, F-wave latency, and associated response waveforms) and a comparison of patient results to normal ranges. Reports are sent to the user by facsimile or e-mail.
An example of application of the generally known NC-stat system is to described in the article “Clinical Utility of the NC-stat System in the Patient with Low Back Pain Point-of-Care Evaluation of Lumbosacral Radiculopathy” by Shai N. Gozani, MD, PhD, excerpted below:
Low back pain is one of the most frequent forms of morbidity in industrialized nations and is the second most common reason for visiting a physician in the United States. While most back pain episodes resolve quickly, a significant number require immediate intervention or develop into chronic conditions. Low back pain, particularly in patients with radiating symptoms or weakness, is often associated with compromise of the lumbosacral nerve roots through mechanical and biochemical means. The diagnostic assessment of the patient with possible radiculopathy may include magnetic resonance imaging (MRI) and electrodiagnostic (EDX) studies. These two modalities are complementary. MRI provides high-resolution visualization of the lumbar soft tissue structures but suffers from high false positive rates. EDX studies have high sensitivity and specificity but may not provide the same degree of localization as MRI. In addition, traditional EDX studies require specialist referral, are expensive, and are uncomfortable for the patient. The NC-stat nerve conduction testing system addresses these to a certain extent issues by providing clinicians with a physiological assessment of the lumbosacral nerve roots and lower extremity nerves, at the point of patient care.
When evaluating patients with low back pain, the NC-stat system is used to assess the distal and proximal neurophysiologic function of the peroneal and tibial nerves. In each test, two types of signals are measured: M-waves and F-waves. Both are myoelectrical potentials evoked by non-invasive electrical stimulation of the appropriate nerve at the ankle. The M-wave is generated by conduction of the neural impulse from the point of stimulation to the innervated muscles and is typically reported as a latency (distal motor latency, DML) and an amplitude. The F-wave response is generated by antidromic (“reverse”) neural propagation from the point of stimulation through the nerve roots into motor neurons of the spinal cord, backfiring of the motor neurons, and then orthodromic (“forward”) conduction to the innervated muscles. The F-wave is a complex signal that may be characterized by a number of different parameters, although in traditional clinical use only the earliest (“minimum”) latency is typically utilized. The NC-stat system incorporates signal processing algorithms that analyze multiple parameters of F-waves.
Neuropathology alters both the M-wave and the F-wave signals. M-wave changes generally indicate disease that is predominately distal, such as entrapment of the nerve at the ankle, or polyneuropathy (e.g. diabetic neuropathy). However, proximal pathology causing axonal loss can also alter M-wave characteristics. The F-wave reflects conduction along the entire length of the nerve and is thus diagnostically sensitive to neuronal injury anywhere from the spinal cord to the inverted muscle, including: nerve root compromise, proximal nerve compression, distal nerve entrapment syndromes, plexopathies, and systemic neuropathies. An overview of the electrodiagnostic interpretation of peroneal and tibial nerve abnormalities as follows:
A normal NC stat Study has an electrodiagnostic interpretation of no electrodiagnostic evidence of nerve root or peripheral nerve pathology. An isolated peroneal Fwave abnormality NC stat Study would have a typical clinical finding of acute or chronic low back/leg pain with an electrodiagnostic interpretation of L5/S1 radiculopathy. An isolated tibial F-wave abnormality NC stat Study would have a typical clinical finding of acute or chronic low back/leg pain based upon an electrodiagnostic interpretation of L5/S1 radiculopathy. A bilateral peroneal and tibial F-wave NC stat Study would have typical clinical findings of chronic low, back and leg pain abnormalities, normal or mild DML abnormalities based upon electrodiagnostic interpretation based on Polyradiculopathy (lumbar stenosis). A bilateral DML and F-wave NC stat Study has a typical clinical finding of foot numbness abnormalities of peroneal and tibial, relative DML changes often greater than F-wave based upon an electrodiagnostic interpretation of Polyneuropathy. A unilateral tibial DML abnormality NC stat Study with a typical clinical finding of foot pain and sensory loss on plantar surface of feet based on electrodiagnostic interpretation of distal tibial neuropathy (tarsal tunnel syndrome). A unilateral peroneal DML abnormality NC stat Study with a typical clinical finding of foot pain and sensory loss in the D1-2 web space based on an electrodiagnostic interpretation of distal peroneal neuropathy. Thus, nerve root involvement is generally indicated by F-wave abnormalities in the presence of normal or mildly altered distal nerve function.
While generally-known systems do provide a clinical tool for diagnosing certain disorders of the peripheral nervous system, these systems have certain limitations in that their diagnostics is confined to certain functionality incorporated into an end-user device. Consequently, a significant need exists for an improved peripheral nervous system (PNS) nerve conduction test apparatus and method for neuromuscular disorders.